Linezolid - a superantibiotic

At the time of their launch, many newly-introduced antibiotics demonstrate
excellent efficacy to treat bacterial infections, including serious diseases.
However, each time a patient takes an antibiotic, the drug may kill most
of the bacteria, but a few of them could survive and later multiply, creating
drug-resistant strains. Recently, drug resistance has been becoming a
major issue, particularly in certain infections such as tuberculosis and
hospital-based staphylococcus infections. About 160 antibiotics are currently
available, and pharmaceutical companies introduce new ones from time to
time, but the new agents usually belong to an existing antibiotic category
and share similar mechanisms of action, thus increasing the chances of
the development of drug resistance. The overprescribing of antibiotics
and improper drug usage may be contributory factors to the development
of resistance.

In this context, linezolid is a particularly interesting antibacterial
because it is the first member of a new class of antibiotics known as
oxazolidinones. This is the first new antibacterial drug class that we
are seeing in decades. Linezolid is indicated for the treatment of nosocomial
infections involving Gram-positive organisms including methicillin-resistant
Staph aureus (MRSA), vancomycin-resistant enterococcus faecium and multi-resistant
strains of Strep pneumoniae. Since gram-positive bacteria are often considered
to be among the greatest challenges in hospital infections, linezolid
will be especially useful because it can be employed to tackle drug resistant
cases where other antibiotics prove to be ineffective. For years, vancomycin
has been employed as a last line of defense against virulent staphylococci,
and vancomycin resistance is a dreaded situation. Linezolid can play a
vital role here. Clinical studies involving more than 4,000 primarily
hospital-treated patients have shown that linezolid is effective in treating
infections caused by Gram-positive bacteria, including resistant infections.
Linezolid also has some activity against other organisms such as Legionella
species, Chlamydia pneumoniae, and Haemophilus influenzae.

The drug is given orally or parenterally. Thus it is possible to continue
oral treatment following initial parenteral therapy, with the benefits
of dosing flexibility and convenience, and the option of completing therapy
as an out patient. Linezolid is generally well tolerated. In clinical
trials, adverse events for patients receiving linezolid and comparator
drugs were similar. Linezolid’s adverse effects include diarrhoea, headache,
nausea and vomiting. These are usually mild to moderate in intensity and
limited in duration.

Linezolid is advocated for use in complicated skin infections and nosocomial
pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA);
concurrent bacteremia associated with vancomycin-resistant Enterococcus
faecium; and concurrent bacteremia associated with community-acquired
pneumonia caused by penicillin-susceptible Streptococcus pneumoniae. The
linezolid brand Zyvox is expected to be an important product for its manufacturer
Pharmacia Upjohn. In view of its efficacy in resistant infections, the
drug has earned the tag of a “superantibiotic”. Doctors believe that linezolid
should be reserved for resistant infections, but the manufacturers suggest
that it could be a first line of therapy. Zyvox sales are expected to
cross $500 million, but at least one analyst believes that if the drug
is used in the way the company wants, annual sales could surpass $1 billion.